crossing96/oncoscreening huggingface dataset:
Molecular and nanoscale evaluation of N-cadherin expression in invasive bladder cancer cells under control conditions or GW501516 exposure.	N-cadherin is a transmembrane glycoprotein expressed by mesenchymal origin cells and is located at the adherens junctions. It regulates also cell motility and contributes to cell signaling. In previous studies, we identified that its anomalous expression in bladder carcinoma was a tumor progression marker. A pharmacological approach to inhibit N-cadherin expression or to block its function could be relevant to prevent disease progression and metastasis development. The morphological exploration of T24 invasive bladder cancer cells by atomic force microscopy (AFM) revealed a spindle-like shape with fibrous structures. By engaging force spectroscopy with AFM tip functionalized with anti-E or anti-N-cadherin antibodies, results showed that T24 cells expressed only N-cadherin as also demonstrated by Western blotting and confocal microscopy. For the first time, we demonstrated by RTqPCR and Western blotting analyses that the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) agonist GW501516 significantly decreased N-cadherin expression in T24 cells. Moreover, high non-cytotoxic doses of GW501516 inhibited confluent T24 cell wound healing closure. By using AFM, a more sensitive nanoanalytical method, we showed that the treatment modified the cellular morphology and diminished N-cadherin cell surface coverage through the decreasing of these adhesion molecule-mediated interaction forces. We observed a greater decrease of N-cadherin upon GW501516 exposure with AFM than that detected with molecular biology techniques. AFM was a complementary tool to biochemical techniques to perform measurements on living cells at the nanometer resolution level. Taken together, our data suggest that GW501516 could be an interesting therapeutic strategy to avoid bladder cancer cell spreading through N-cadherin decrease.	bladder
Exosome-Derived LINC00960 and LINC02470 Promote the Epithelial-Mesenchymal Transition and Aggressiveness of Bladder Cancer Cells.	Exosomes are essential for several tumor progression-related processes, including the epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.	bladder
Association of arsenic with recurrence of urinary bladder cancer.	Arsenic is known to be an important aetiological factor for the development of urinary bladder cancer. It is known to be found excessively in ground water in certain geographical areas, including West Bengal. We have studied patients with recurrent bladder cancer from different areas of this Indian state and correlated arsenic as a causative aetiological factor for development and aggressiveness of the biological behaviour of urinary cancer. We included 31 patients from various parts of West Bengal state with recurrent bladder cancer who were operated in our institute. Their clinical and residential data and their arsenic content of tumour tissue were measured. Statistical analysis was performed to test the association of tissue arsenic with clinicopathological features of recurrent disease. We found very high levels of arsenic in tumour tissue in all residents of the districts with high prevalence of arsenic in the drinking water. We also observed more aggressive clinicopathological progression and early recurrence in patients with high arsenic content. We conclude that arsenic is a causal factor in the clinicopathological progression of recurrent urinary bladder cancer. Measures to decrease the level of arsenic in drinking water should be taken as this may both improve clinicopathological outcomes in the recurrence of urinary bladder carcinoma, as well as reducing its overall incidence.	bladder
Platinum(II) ring-fused chlorins as efficient theranostic agents: Dyes for tumor-imaging and photodynamic therapy of cancer.	The discovery of Pt-chlorin-type theranostic agents is described. Luminescent Pt(II) 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, with different degrees of hydrophilicity, have been synthesized and their in vitro photocytotoxicity against human melanoma, oesophageal and bladder carcinomas was studied. A di(hydroxymethyl)-substituted chlorin was identified as a privileged molecule to explore imaging-guided photodynamic therapy. In addition to the high activity as PDT agent and absence of cytotoxicity per se, this molecule showed the ideal photophysical and photochemical properties. In vivo studies using a A375 melanoma mouse model, proved the extraordinary properties of this chlorin as a luminescent probe and the ability to impair tumor growth, making image guided treatment and follow up a possibility.	bladder
Myoepithelial Carcinoma of Urinary Bladder in a Pediatric Patient. A Case Report.	Myoepithelial carcinoma is a rare pathological variant, usually expressed in salivary gland. This case report describes a case of pediatric myoepithelial carcinoma in the urinary bladder. A 4-year-old male patient was admitted to a specialized hospital in Lima, Peru for hematuria. A CT scan showed a tumor lesion in the bladder wall, and biopsy revealed myoepithelial carcinoma of urinary bladder. Six courses of chemotherapy + partial cystectomy + radiotherapy was completed. The treatment was defined based on the pathological variant and the tumor location. The patient is currently at 2 years of disease-free survival.	bladder
To Radiate or Not to Radiate-The Challenges of Pelvic Reirradiation.	Patients who receive pelvic radiation are at risk for both local recurrences of their primary malignancy or for the development of a new malignancy in the irradiated pelvic structures. The management of postirradiation pelvic tumor is complicated and can be associated with both poor prognosis and significant morbidity. Historically, reirradiation within the pelvis was never entertained as part of treatment management due to concern for severe toxicity and exceeding of normal-tissue tolerances. However, it may play a role with modern techniques and careful patient selection. The following case and accompanying expert opinions demonstrate some of the key considerations for pelvic reirradiation as a treatment option.	bladder
Prognostic significance of previous tonsillectomy after radical cystectomy for bladder cancer.	Introduction: To examine whether previous tonsillectomy (TE) impacts on survival after radical cystectomy (RC) for bladder cancer (BC).Patients and Methods: A total of 320 patients were staged cM0 and underwent RC for BC between 2002 and 2013. We retrospectively investigated whether patients had undergone TE prior to RC. Chi-square/Fisher-Exact test was carried out to compare clinicopathological features between the TE- and non-TE-group. Kaplan-Meier analysis with log-rank test was used to estimate recurrence-free survival (RFS) and multivariable Cox-regression analysis of risk factors of recurrence. The median follow-up was 31 months (interquartile range: 9-54).Results: A history of TE was present in 18 of the 320 patients (5.6%). All TEs were performed for benign conditions. TE prior to RC was associated with a history of appendectomy (p = 0.045), lower age at RC (p = 0.029), tumor unifocality (p < 0.001), advanced histopathological tumor stage (p = 0.015), non-pure urothelial carcinoma (p = 0.025), lymphovascular invasion (p = 0.035) and receipt of palliative chemotherapy (p = 0.004). The 3-year RFS was 39.2% for patients with previous TE and 62.4% for those without (p = 0.008). In multivariable analysis, adjusted for all significant parameters of univariable analysis, lymph-node tumor involvement (p = 0.017), positive surgical margins (p = 0.047), tumor grade (p = 0.032), advanced tumor stage (≥pT3a; p = 0.049) and a history of TE (p = 0.021) remained independent prognosticators of recurrence.Conclusion: In this series, previous TE was an independent predictor of recurrence after RC for BC. Further studies are needed to assess whether TE induces immunological alterations that might exert adverse effects on cancer progression of patients with invasive BC.	bladder
[First-line treatment of metastatic urothelial carcinoma : Update immuno-oncology].	The first-line therapy of metastatic bladder cancer (urothelial carcinoma, UC) depends on whether a patient is cisplatin-fit or not. Cisplatin-fit patients should be treated with the standard chemotherapy protocol GC (gemcitabine/cisplatin) or alternatively MVAC (methotrexate/vinblastine/doxorubicin/cisplatin). The optimal first-line therapy for cisplatin-unfit patients remains unclear due to the lack of high level of evidence. One criterion for selecting therapy can be the PD-L1 (programmed cell death ligand 1) status of the tumor. The PD-L1-negative patients (PD-L1 <5% for atezolizumab and combined positivity score [CPS] <10 for pembrolizumab) seem to have a greater benefit from the combination chemotherapy GCa (carboplatin/gemcitabine). The PD-L1-positive patients (PD-L1 ≥5% or CPS ≥10) on the other hand may have a greater benefit from and a longer response to the two immune checkpoint inhibitors that are currently approved for this indication, namely atezolizumab and pembrolizumab. Two phase 3 trials that compare head-to-head immunotherapy alone or in combination with chemotherapy vs. chemotherapy alone may help to define the optimal first-line therapy for metastatic UC. Preliminary data from one of these studies indicate an advantage for the combination of immunotherapy with chemotherapy in all subgroups.	bladder
Establishment of diagnostic criteria for upper urinary tract urothelial carcinoma based on genome-wide DNA methylation analysis.	The aim of this study was to develop a less invasive and accurate diagnostic system for upper urinary tract urothelial carcinoma (UTUC) based on genome-wide DNA methylation profiling. Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analysed 26 samples of normal control urothelial tissue (C), an initial cohort of 62 samples (31 samples of non-cancerous urothelium [N] from UTUC patients and 31 samples of the corresponding UTUCs), a validation cohort of 82 samples (41 N and 41 UTUC samples), and 14 samples of urinary bladder urothelial carcinoma (BUC). In the initial cohort, we identified 2,448 CpG sites showing significant differences in DNA methylation levels between both C and UTUC and N and UTUC, but not showing differences between C and N. Among these CpG sites, 10 were located within CpG islands or their shores and shelves included in genomic domains where DNA methylation levels are stably controlled, allowing discrimination of UTUC even from BUC. Receiver operating characteristic curve analysis for discrimination of UTUC from N in these 10 CpG and neighbouring sites (37 diagnostic panels in total) yielded area under the curve values of 0.959-1.000, with a sensitivity and specificity of 86.6-100% and 93.5-100%, respectively. The diagnostic impact was successfully confirmed in the validation cohort. Our criteria were useful for diagnosis of UTUC, regardless of its clinicopathological features. Application of our criteria to voided urine samples will ultimately allow non-invasive DNA methylation diagnosis of UTUC.	bladder
Xanthogranulomatous Ureteritis Mimicking Ureteral Involvement by Cancer in a Radical Cystectomy Specimen.	Xanthogranulomatous pyelonephritis is well established as a renal mass-forming inflammatory process. However, a ureteral counterpart is minimally recognized. In this article, we present a case of xanthogranulomatous ureteritis in an 81-year-old woman, mimicking ureteral involvement by cancer in a radical cystectomy specimen for invasive urothelial carcinoma. Similar to the pathogenesis of xanthogranulomatous pyelonephritis, the patient was noted to have ureteral obstruction by calculus and had urine culture positive for Klebsiella pneumoniae. To our knowledge, this is the first report of xanthogranulomatous ureteritis associated with this pathogen and the only report associated with concurrent bladder cancer. Increased pathologist and urologist awareness of xanthogranulomatous ureteritis expands the spectrum of pseudotumoral processes of the ureter.	bladder
Gambogenic acid suppresses bladder cancer cells growth and metastasis by regulating NF-κB signaling.	BACKGROUND: Gambogenic acid (GNA) is one of the main active components of Gamboge, and its anticancer role has been reported in some cancers. The study was to investigate the inhibitory effects of GNA on the proliferation and metastasis of bladder cancer (BC) cells and its potential regulatory mechanisms. MATERIALS AND METHODS: BC cell lines (BIU-87 cells, T24 cells, and J82 cells) were treated with different doses of GNA for different time, and then the effects of GNA on BC cell were examined in vitro using CCK-8 assay, apoptosis assays, and Transwell tests. NF-κB signaling activity was detected by the NF-κB p65 luciferase reporter assay. Western blot was used to detect the expressions of cIAP2, XIAP, Survivin, and p65. RESULTS: GNA inhibited the viability of BC cells in vitro in a dose- and time-dependent manner and facilitated apoptosis of BC cells. Moreover, GNA could remarkably impede the migration and invasion abilities of BC cells. In terms of mechanism, GNA administration reduced the activity of NF-κB signaling and down-regulated the expressions of p65, survivin, XIAP, and cIAP2. CONCLUSION: GNA blocks the growth and metastasis of BC cells via inhibiting the NF-κB signal transduction pathway.	bladder
Inhibitory effect of ergosterol on bladder carcinogenesis is due to androgen signaling inhibition by brassicasterol, a metabolite of ergosterol.	We previously revealed that Choreito, a traditional Kampo medicine, strongly inhibits bladder carcinogenesis promotion. We have also shown that Polyporus sclerotium, which is one of the crude drugs in Choreito, has the strongest bladder carcinogenesis inhibitory effect and that the ergosterol contained in Polyporus sclerotium is the main active component. In this study, we analyzed the mechanism by which ergosterol inhibits bladder carcinogenesis. Rats were given an N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) solution ad libitum, and then a promoter [saccharin sodium (SS), DL-tryptophan, or BHBN] was administered together with ergosterol or its metabolite, brassicasterol. The bladders were removed from rats, and the inhibitory effect on carcinogenesis promotion was evaluated by an agglutination assay with concanavalin A (Con A). Although the oral administration of ergosterol inhibited the promotion of bladder carcinogenesis with SS, the intraperitoneal administration of brassicasterol showed a stronger effect. The effect of brassicasterol on carcinogenesis promotion was observed regardless of the type of promoter. Administration of testosterone to castrated rats increased the number of cell aggregates caused by Con A. In contrast, intraperitoneal administration of brassicasterol to castrated rats treated with testosterone significantly decreased the number of cell aggregates, confirming the inhibition of bladder carcinogenesis promotion. The inhibitory effect of ergosterol on bladder carcinogenesis is due to brassicasterol, a metabolite of ergosterol. The action of brassicasterol via androgen signaling may play a role in the inhibitory effect on bladder carcinogenesis promotion.	bladder
Boosting bladder cancer treatment by intravesical nitazoxanide and bacillus calmette-guérin association.	PURPOSE: Nitazoxanide (NTZ) has shown a promising antitumoral effect, the current study compared the anti-neoplastic effects of intravesical NTZ and BCG plus NTZ in NMIBC animal model. METHODS: 30 rats, Fisher 344 were instilled with 4 intravesical doses of 1.5 mg/kg of N-methyl-N-nitrosourea (MNU) every 15 days for BC induction. The animals were divided into 3 groups (Group BCG 10(6) UFC - 1 mg of BCG; Group NTZ - 300 mg/kg of NTZ; Group NTZ + BCG - simultaneous treatment of BCG and NTZ) and received weekly intravesical treatment for 6 consecutive weeks. Animals were submitted to ultrasound imaging and euthanasia, their bladders were collected and histopathological, immunohistochemical tests (ki67 e c-Myc) and Western Blotting (PI3K, mTOR, and p-4E-BP) were performed. RESULTS: Histopathological tests showed 66.67%, 62.5% and 37.5% incidence of BC in animals treated with BCG, NTZ, and NTZ + BCG, respectively. Nuclear positivity for ki-67 in BC animals were 12.4% (IC 10.1-14.6%), 13.2% (IC 10.5-15.9%) and 8.8% (IC 6.0-11.6%) in BCG, NTZ and NTZ + BCG group, respectively (p = 0.063). Between animals with carcinoma, c-Myc strong positive was 40.10% in NTZ, 32.2% in BCG and 19.90% in the NTZ + BCG group (p < 0.001). Blotting has shown mTOR (p = 0.0473) and PI3K inhibition (p = 0.0349) in the presence of BCG, added to 4-EBP inhibition in the presence of NTZ (p = 0.0004). CONCLUSIONS: Results show the possible synergy between the gold standard BC treatment BCG and NTZ, in which multiple targets inhibition such as c-Myc and downstream mTOR, p-4E-BP and PI3K might play a role.	bladder
Mitotic activity index and CD25+ lymphocytes predict risk of stage progression in non-muscle invasive bladder cancer.	In urothelial cell type non-muscle invasive urinary bladder carcinoma, TNM stage and WHO grade are widely used to classify patients into low and high‑risk groups for prognostic and therapeutic decision-making. However, stage and grade reproducibility and prediction accuracy are wanting. This may lead to suboptimal treatment. We evaluated whether proliferation features, nuclear area of the epithelial cancer cells and the composition of stromal and tumor infiltrating lymphocytes have independent prognostic value. In 183 primary non-muscle invasive bladder cancer patients with long follow-up (median for stage progression cohort: 119 months, range 5-173; median for tumor recurrence cohort: 82, range 3-165) proliferation features Ki67, PPH3 and Mitotic Activity Index (MAI), Mean Nuclear Area (MNA), lymphocyte subsets (CD8+, CD4+, CD25+) and plasma cells (CD138+) were assessed on consecutive sections. Post-resection instillation treatments (none, mitomycin, BCG) were strictly standardized during the intake period. Risk of recurrence was associated with expression of Ki67 (≤ 39 vs. > 39) and Multifocality (p = 0.01). Patients with low Ki67 had a higher recurrence rate than those with high Ki67. Lymphocyte composition did not predict recurrence. Stage progression was strongly associated with high values for MAI (>15) and CD25+ (>0.2%). In a multivariate analysis the combination of MAI and CD25+ was the single most prognostic feature (p<0.001). Validation of these results in additional, independent studies is warranted.	bladder
Death-inducer obliterator 1 (DIDO1) silencing suppresses growth of bladder cancer cells through decreasing SAPK/JNK signaling cascades.	Death inducer obliterator (DIDO) is involved in apoptosis and embryonic stem cell self-renewal. Here, we investigate the effect of DIDO1 on bladder cancer cells and clarify the underlying molecular mechanism. Bladder cancer tissues and cell lines (T24, ScaBER, 5637), as well as normal bladder epithelial cells (SV-HUC-1), were used to measure the levels of DIDO1 mRNA and protein by qRT-PCR and western blot, respectively. The results indicated that DIDO1 was highly expressed in bladder cancer tissues and cell lines. And the expression of DIDO1 in T24 and 5637 cells was higher than that in ScaBER and SV-HUC-1 cells. The expression of DIDO1 was knocked down in T24 and 5637 cells by infection with shDIDO1-1 and shDIDO1-2 lentivirus. The growth of T24 and 5637 cells was monitored using Celigo, MTT assays, and colony formation assay. Apoptosis was examined by flow cytometric analysis. The effect of DIDO1 knockdown on tumorigenesis of T24 xenograft tumors was determined in nude mice. Reduction of DIDO1 mRNA resulted in reduced proliferation, decreased cell colony formation, increased apoptosis in vitro, and inhibited tumorigenesis in vivo. Furthermore, we identified signaling molecules involved in stress and apoptosis using the PathScan Antibody Array Kit and western blot. The depletion of DIDO1 significantly decreased the levels of phosphorylated SAPK/JNK, and Chk1/2, as well as the upregulating cleaved Caspase-7 expression. These results indicated that the potential mechanism of DIDO1 action might involve SAPK/JNK signaling cascades.	bladder
Photoactivated H(2) Nanogenerator for Enhanced Chemotherapy of Bladder Cancer.	Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H(2) nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H(2) production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H(2) gas in situ upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H(2) gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H(2) evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.	bladder